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United States Patent (10) Patent No.: US 6,413,571 Bl Liu (45) Date of Patent: Jul

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United States Patent (10) Patent No.: US 6,413,571 Bl Liu (45) Date of Patent: Jul I1111111111111111 11111 lllll 111111111111111 111111111111111 1111111111 11111111 US006413571Bl (12) United States Patent (10) Patent No.: US 6,413,571 Bl Liu (45) Date of Patent: Jul. 2, 2002 (54) STEROL ESTERS OF CONJUGATED Abstract from DATABASE CHEMABS Online!. Chemical LINOLEIC ACIDS AND PROCESS FOR Abstracts Service, Columbus, OH, US; Kaoru, Kazuhisa et THEIR PRODUCTION al: "Conjugated linoleic acid esters as antioxidants, their manufacture, and antioxidants and food containing the (75) Inventor: Linsen Liu, Irvine, CA (US) esters" retrieved from STN Database accession No. 133:221697 XP 002167426 abstracted from JP 2000 247965 (73) Assignee: The Board of Regents for Oklahoma A, (Snow Brand Milk Products Co., Ltd., Japan) Sept. 12, State University, Stillwater, OK (US) 2000. ( *) Notice: Subject to any disclaimer, the term of this Abstract of Dyas, L. et al.: "Steryl fatty acyl esters in patent is extended or adjusted under 35 plants", Phytochemistry, Sept. 1993, v. 34(1) pp. 17-29. U.S.C. 154(b) by O days. Abstract of Field, F. et al.: "Effect of micellar beta-sitosterol (21) Appl. No.: 09/693,562 on cholesterol metabolism in CaCo-2 cells", Journal of Lipid Research, Feb. 1997, v. 38(2) pp. 348-360. (22) Filed: Oct. 20, 2000 Abstract of Gylling, H. Siimes, et al.: "Sitostanol ester Related U.S. Application Data margarine in dietary treatment of children with familial (60) Provisional application No. 60/160,894, filed on Oct. 21, hypercholesterolemia", Journal of Lipid Research, Aug. 1999. 1995, V. 36(8) pp. 1807-1812. (51) Int. Cl.7 ................................................ A23D 9/007 Abstract of Micich, T.J. et al.: "Polymer-supported (52) U.S. Cl. ....................... 426/611; 552/544; 552/547; saponins: an approach to cholesterol removal from but­ 552/554; 554/174 teroil", Journal of Agricultural and Food Chemistry, Aug. (58) Field of Search .......................... 426/611; 552/544, 1992, V. 40 (8) pp. 1321-1325. 552/545, 547,554; 514/170, 171, 182, 562; 554/174; 435/134, 135 Haumann, Barbara F.: "Conjugated linoleic acid offers research promise", Inform, 1996, pp. 152-153, 156-159, (56) References Cited vol. 7, No. 2. U.S. PATENT DOCUMENTS O'Shea, M. et al.: "Conjugated linoleic acid in bovine milk 5,502,045 A 3/1996 Miettinen et al. fat: a food-based approach to cancer chemoprevention", 5,554,646 A 9/1996 Cook et al. Trends in Food Science & Technology, 1998, pp. 192-196, 5,760,082 A 6/1998 Cook et al. vol. 9, Elsevier Science Ltd. 5,892,068 A 4/1999 Higgins, III 5,919,451 A 7/1999 Cook et al. "Phytosterols", Critical Reviews in Food Science and Nutri­ 6,031,118 A * 2/2000 van Amerongen et al. 552/544 tion, 1999, pp. 275-283, vol. 39, No. 3, CRC Press LLC. 6,106,886 A * 8/2000 van Amerongen et al. 426/611 6,123,979 A * 9/2000 Hepburn et al. ............ 426/611 Steinhart, Carol: "Conjugated LinoleicAcid the Good News 6,139,897 A * 10/2000 Goto et al. ................. 426/601 about Animal Fat", Journal of Chemical Education, 1996, p. 6,147,236 A * 11/2000 Higgins, III. ............... 552/554 A302, vol. 73, No. 12. 6,231,915 Bl * 5/2001 van Amerongen et al. 426/611 2002/0010349 Al * 1/2002 Roden * cited by examiner FOREIGN PATENT DOCUMENTS DE 197 50 422 C 1 11/1998 .............. C07J/9/00 Primary Examiner-Carolyn Paden EP 0 982 316 A 3/2000 .............. C07J/9/00 (74) Attorney, Agent, or Firm-Fellers, Snider, WO WO98/38206 * 9/1998 Blankenship, Bailey & Tippens, P.C. WO WO 99/56558 11/1999 OIBER PUBLICATIONS (57) ABSTRACT J. Agricultural and Food Chem 49(11)5210-5216. * Novel sterol/stanol esters of a conjugated fatty acid are Abstract from DATABASE BIOSIS Online!. BIO­ provided through the esterification or transesterification of a SCIENCES INFORMATION Service, Philadelphis, PA, sterol such as beta-sitosterol or a hydrogenated form thereof US; May 1999 (1999-05); Gylling Helena et al: "Choles­ (stanol). Such novel esters exhibit the combined properties terol reduction by different plant stanol mixtures and with normally possess by the sterol/stanol compound and the variable fat intake." Database access10n No. conjugated fatty acid and as such are excellent additives for PREV199900281083 XP002167425 abstracted from dietetic foods and supplements. Metabolism Clinical and Experimental, vol. 48, No. 5 May 1999, pp. 575-580. ISSN: 0026-0495. 10 Claims, No Drawings US 6,413,571 Bl 1 2 STEROL ESTERS OF CONJUGATED of a sterol or stanol with a conjugated fatty acid, such as LINOLEIC ACIDS AND PROCESS FOR CLA, there is provided a compound which provides the THEIR PRODUCTION advantages of both the conjugated fatty acid and the sterol or stanol. CLA is a liquid fatty acid with two conjugated CROSS REFERENCE TO RELATED 5 double bonds, therefore, it can reduce the melting point of APPLICATION sterols and stanols dramatically. Indeed, the beta-sitosterol This application claims the benefit of my copending U.S. ester of CLA is liquid at ambient temperature while the provisional application Serial No. 60/160,894, filed Oct. 21, current commercial products made of the fatty acids derived 1999. from vegetable oils are solid or semisolid. The sterol ester of 10 CLA also provides a product having lower total calories than BACKGROUND OF THE INVENTION the blended product that provides the same doses of sterol and CLA. Such new products thus offer the combined 1. Technical Field benefits of sterols/stanols as a cholesterol control agent and This invention relates to novel sterol esters of conjugated CLA as an anticarcinogen and fat reducing agent. Such linoleic acids and a process for the production of the same 15 esters can be used as a supplement or ingredient in foods. by esterification of sterols and stanols with a conjugated In accordance with another embodiment of the present, linoleic acid. sterol esters can be readily prepared through esterification of 2. Background sterol or stanol with the conjugated fatty acid or by trans­ It is known that the addition of plant sterol (phytosterol) esterification of sterol or stanol with of the conjugated fatty to diets will reduce serum cholesterol levels. Such additives 20 acid methyl ester. Transesterification is the preferred method effect the reduction of serum cholesterol through the dis­ to those skilled in the art. ruption of intestinal absorption of dietary cholesterol by A better understanding of the present invention, its several displacing it from bile and micelli. Free sterols or stanols, aspects, and its advantages will become apparent to those though, are not optimum candidates for use in typical skilled in the art from the following detailed description, pharmaceutical or dietary dosage forms as cholesterol reduc- 25 wherein there is shown and described the preferred embodi­ ing agents due to their very high melting points 130 C. and ment of the invention, simply by way of illustration of the low solubility in aqueous and oil media. As a result such best mode contemplated for carrying out the invention. compounds are preferred to be converted into their fatty esters for food applications, which reduce their melting DETAILED DESCRIPTION OF THE points and solubility in oil. However, the fatty acids attached 30 PREFERRED EMBODIMENT to sterol in the current commercial products are from veg­ As used herein the term "sterol ester" includes both the etable oil such as sunflower, canola, or soybean oil. Those plant sterol ester per se as well as the hydrogenated sterol fatty acids provide no pharmaceutical or nutraceutical func­ products which are referred to as stanol and campestanol. tions except increasing the total calories of the products. Such compounds have the following general formula: 35 Conjugated fatty acids are known to have many health Ac---C0---0-ST benefits such as reducing body fat, inhibiting tumor growth and reducing atherosclerosis. Such conjugated fatty acids wherein Ac-CO is an acyl group from a conjugated fatty are naturally found in beef and dairy fats in trace amounts acid and O-ST is a steryl group derived from a sterol/ (0.2-30 mg/g food). One such conjugated fatty acid is stanol. conjugated linoleic acid ( octadecadienoic acid), hereinafter 40 The term "conjugated fatty acid" is intended to refer to referred to as CLA. Cattle convert the linoleic acid in grass conjugated linoleic acid (CLA) which in turn refers to a into CLA by their special digestive processes. However, group of geometrical and positional isomers of linoleic acids since humans cannot produce such conjugated fatty acids, including but not limited to 9,11-octadecadienoic acid, and such additives to the human system must be through the diet. 10---12 octadecadienoic acid. The cis-9, trans-11 isomer is Thus the providing of CLA in a form to permit its use in 45 the most dominant isomer of CLA in dairy products and is dietetic foods would serve as a significant contribution to the also the most biologically active form as known at present. The term "sterol" or "sterol/stanol" as used herein is field of dietetic foods since it would enable the recipient to receive a valuable additive since it is known that CLA is intended to mean the sterol compound per se or its hydro­ effective in increasing body protein or preventing the loss of genated form including stanol and campestanol. body protein in a human, increasing food efficiency in 50 The present invention is based upon my discovery that humans and assists in reducing body fat. through the use of the conjugated fatty acid-CLA-in the esterification of a sterol there is obtained a product which is It is thus an object of the present invention to provide a liquid at ambient temperature and which product has lower novel ester composition consisting essentially of phytoster­ total calories and which product provides the combined ols including plant sterols/stanols and conjugated linoleic 55 benefits of cholesterol control agent and an anticarcinogen acids.
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